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BackgroundInsulin resistance is strongly associated with the development of type 2 diabetes and cardiovascular disease. However, the underlying mechanisms linking insulin resistance and the development of atherosclerosis have not been fully elucidated. Moreover, the protective effect of antihyperglycemic agent, metformin, is not fully understood. This study investigated the protective effects and underlying mechanisms of metformin in balloon-injury induced stenosis in insulin resistant rats.MethodsAfter 4 weeks high fructose diet, rats received balloon catheter injury on carotid arteries and were sacrificed at 1 and 4 weeks post injury. Biochemical, histological, and molecular changes were investigated.ResultsPlasma levels of glucose, insulin, total cholesterol, triglyceride, free fatty acids, and methylglyoxal were highly increased in fructose-induced insulin resistant rats and treatment with metformin significantly improved this metabolic profile. The neointimal formation of the carotid arteries was enhanced, and treatment with metformin markedly attenuated neointimal hyperplasia. A significant reduction in BrdU-positive cells in the neointima was observed in the metformin-treated group (P < 0.01). Insulin signaling pathways were inhibited in insulin resistant rats while treatment with metformin enhanced the expression of insulin signaling pathways. Increased expression of JNK and NFKB was suppressed following metformin treatment. Vasoreactivity was impaired while treatment with metformin attenuated phenylephrine-induced vasoconstriction and enhanced methacholine-induced vasorelaxation of the balloon injured carotid arteries in insulin resistant rats.ConclusionThe balloon-injury induced neointimal formation of the carotid arteries is enhanced by insulin resistance. Treatment with metformin significantly attenuates neointimal hyperplasia through inhibition of smooth muscle cell proliferation, migration, and inflammation as well as by improvement of the insulin signaling pathway.

Abnormal mitochondria have long been hypothesized to be involved in tumorigenesis. Mitochondrial DNA (mtDNA) mutations have been found in various cancer cells, yet their role in tumorigenesis remains largely unknown. Our long-term goal is to understand the role of mtDNA polymorphism and mtDNA mutations in tumorigenesis. We focused on the role of the mtDNA haplogroup; a 4,977 bp common mtDNA deletion; mtDNA mutations in the main control region of mtDNA or displacement loop; and mtDNA heteroplasmy in cancer occurrence and cancer development. Our results indicate that qualitative and quantitative changes in mtDNA play an important role in cancer development.

BackgroundMolecular epidemiological studies have shown that gene polymorphisms of vitamin D receptor (VDR) are associated with prostate cancer risks. However, previous results from many molecular studies remain inconsistent.MethodsBlood samples were collected from 122 prostate cancer patients and 130 age-matched control subjects in the Han population of Southern China. The differences of VDR gene polymorphism between cancer cases and controls were determined by PCR-RFLP, examiming FokI (exon 2), BsmI, Tru9I, ApaI (intron 9), and TaqI (exon 9). Associations between the VDR gene polymorphism and prostate cancer risk were calculated in an unconditional logistic regression model. Linkage disequilibrium and haplotypes were analyzed with the SHEsis software.ResultsOf five polymorphisms, BsmI was shown to associate with prostate cancer, while FokI, Tru9I, ApaI, and TaqI did not show any significant association. After adjustment for age, the BsmI 'B' allele was associated with an almost 1/3-fold risk (OR = 0.35, 95%CI: 0.15-0.80) of the occurrence of prostate cancer, a 1/5-fold risk (OR = 0.20, 95%CI: 0.06-0.68) of poorly differentiated prostate cancer, and a 1/10-fold risk (OR = 0.10, 95%CI: 0.01-0.78) of aggressive prostate cancer compared with the 'b' allele, especially among older men (>71 years). In addition, haplotype analysis revealed that the 'F-b-U-A-T' was more frequent found in cases than in controls (3.4% vs 0.0%, P = 0.0035), while the frequency of haplotype 'F-B-U-a-T' was 0.8% in cases, significantly lower than in controls (3.9%, P = 0.019).ConclusionOur experiments provide evidences that genetic polymorphisms in the VDR gene may be potential risk factors for prostate cancer in the Han population of southern China and the susceptibility to prostate cancer is associated with ethnicity and geographic location.